| Expression pattern: |
DN |
| Associated gene: |
TRIM28, MDM2, p53, p21, Bax |
| Associated microRNA: |
- |
| Biological function: |
Suppresses FLT3-ITD AML cell proliferation and leukemia maintenance, promotes apoptosis, reduces leukemia stem/initiating cell self-renewal, and enhances sensitivity to quizartinib treatment. |
| Molecular mechanism: |
CircTADA2A competitively binds TRIM28, inhibits TRIM28/MDM2 complex formation, reduces p53 ubiquitination and proteasomal degradation, stabilizes p53 protein, and activates the p53 pathway. |
| Biological pathway or process: |
p53 signaling (promotes); apoptosis (promotes); proliferation (inhibits); cell cycle (inhibits); ubiquitination (inhibits); drug resistance (inhibits); other pathway/process (inhibits) |
| Detected method: |
Q
M
|
| Validation methods: |
Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Sanger Sequencing; Actinomycin D / DRB Stability Assay; RT-qPCR; Microarray; FISH / smFISH; Nuclear-Cytoplasmic Fractionation; Clinical Sample Validation; RIP (RNA Immunoprecipitation); RNA Pull-Down; Co-IP; Transfection; CCK8; Colony Formation Assay; Flow Cytometry(Non-apoptosis/cycle); Western Blot; In Vivo Animal Model; IHC (Immunohistochemistry); Bioinformatics Analysis |
| Clinical significance: |
CircTADA2A is proposed as a potential therapeutic molecule and RNA-based therapeutic approach for FLT3-ITD AML treatment, including enhancement of quizartinib response. |
| Description: |
CircTADA2A is downregulated in FLT3-ITD AML and functions as a tumor-suppressive circRNA. It binds TRIM28 to disrupt TRIM28/MDM2 complex formation, reduces p53 ubiquitination and degradation, activates the p53 pathway, suppresses AML cell proliferation and leukemia-initiating capacity, and enhances quizartinib response. |
| Confidence score: |
0.8814 |